Created: Jan. 1995
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About Bladder InstillationsDuring a bladder instillation, the bladder is filled with a therapeutic solution that flows in through a narrow tube inserted through the urethra and into the bladder, called a catheter. The instillation is held for varying periods of time, from a few seconds to 15 minutes or more (known as "dwell time"), before being drained or voided. Although most physicians use the "adult" size catheters, if patients have discomfort or difficulty with it, they can request the use of a smaller "pediatric" catheter.
The purpose of the instillation varies, depending on what is instilled. Some solutions are thought to coat and protect the bladder, while others are thought to suppress inflammation. Many physicians instill combinations of ingredients that they believe work better than a single agent. Patients sometimes refer to these as "cocktails."
IC patients may want to ask their doctor to describe all of the ingredients in the instilled solution, and what each is for. This knowledge is important because many IC patients have drug allergies and sensitivities. Should you have a reaction to one of the components, your doctor can adjust the combination to suit your particular needs.
Dimethyl sulfoxide was the first of two therapies approved by the US FDA for the treatment for IC in the early 1970's. Its use, however, has quickly diminished due to the growing popularity of Rescue Instillations and research that suggests that DMSO can be damaging to the bladder muscle. Many clinics no longer use DMSO treatments.
DMSO is a dilute, sterile, and purified version of a chemical that was used for many years as an industrial solvent before being found to have anti-inflammatory, analgesic, muscle relaxant, mast cell stimulation and collagen dissolution properties. The FDA has approved a solution of DMSO (brand name: RIMSO-50) for bladder instillation in treating IC. It is thought to work by reducing inflammation and is estimated to be effective in about 50% of cases
Research presented in 2002 at the AUA Annual Meeting now suggests that DMSO has the potential of causing damage to the muscle of the bladder when used at the 50% dosage. In "DMSO - Does it change functional properties in the bladder wall" (Diethild Melchior*, C Subah Packer, Tomalyn C Johnson, Martin Kaefer, Indianapolis, IN) researchers tested various concentrations of DMSO on strips of bladder muscle to try to determine what, if anything, the DMSO did to muscle. They found that DMSO triggered intense muscle contractions and, at doses higher than a 30% solution, caused what appeared to be long-lasting contractions that could be irreversible. Since the normal FDA approved dosage used for humans is 50%, researchers suggested that the dosage be reduced to, at most, 25% to avoid any possibility of muscle damage.
A course of treatment involves six to 8 weekly instillations. Usually, patients will have one to two courses of therapy. DMSO is rarely used as a long term therapy, particularly if patients show no response to treatment.
DMSO is administered via catheterization after the urethra has been anesthetized with a 2% lidocaine jelly. Once it is placed into the bladder, patients are instructed to hold the medication for 15-20 minutes before urinating.
Some patients who respond to DMSO notice improvement of symptoms immediately. Others improve three or four weeks after the six to eight week cycle of treatments. If improvement is seen, the cycle can be repeated according to the needs of the patient.
A few patients experience intense burning or an exacerbation of symptoms for a short time after the first treatment (the result of mast cell stimulation), which often subsides. Many of these patients see improvement in their IC symptoms after subsequent treatments. Many experience no discomfort. The most common side effect is a garlic-like taste in the mouth and an odor to the breath and body, occurring a few hours after instillation and continuing for about a day (2). About 10% of patients report bladder spasms and irritability (3). The manufacturer of RIMSO-50 strongly recommends that patients have "slit-lamp eye examinations" before and after treatment to verify that no eye lens opacity (clouding) has occurred with treatment. DMSO is teratogenic in animals. It should not be used during pregnancy, within four weeks of a bladder biopsy or if infection is present (4).
DMSO research studies report a 35-40% relapse rate after a 4-8 week course of treatment. However, 50-60% of those patients responded favorably to additional DMSO treatments (1). For those who relapse, DMSO may be administered in one to two month intervals (maintenance therapy), depending upon their symptoms. If patients do not respond to DMSO initially, it may be combined with hydrocortisone, heparin and sodium bicarbonate. Please check the on-line ICN research library for the latest research studies on DMSO.
Heparin is instilled in the bladder via catheter in a manner similar to DMSO. While it is usually done in a doctor's office at first, most patients find they can easily learn to self-catheterize for home treatment. Research by Parsons (5) shows that heparin, when administered three times per week for three months resulted in clinical remission of symptoms in 56% of patients and the remission was maintained in 80%-90% for up to one year, if treatment was continued at a maintenance level.
It is common for DMSO and heparin to be instilled in the bladder together. Heparin instillations are also often used in a treatment program that includes oral ELMIRON®. Please check the ICN Research Library for the latest research studies on heparin.
The main ingredient in Cystistat is hyaluronic acid. Hyaluronic acid occurs naturally in the connective tissues of the human body and has many properties in common with other drugs used in the treatment of IC, such as heparin and ELMIRON. A form of hyaluronic acid has been used for many years to protect against corneal loss during eye surgery. It is believed that Cystistat coats the lining of the bladder and protects it from irritating substances in the urine.
It is instilled directly into the bladder via catheter in a doctor's office. Bioniche recommends that patients receive the first four treatments on a weekly basis, followed by one treatment monthly until symptoms resolve. Most people don't experience relief until the fifth or sixth treatment. Preliminary studies found that most patients had symptomatic improvement after 12 weeks. Long-term trials need to be completed in order to better evaluate its effectiveness.
Cystistat has not been approved by the FDA, however, it is available on a limited basis to IC patients in both Canada and the US. To find out more about Cystistat's availability, Bioniche can be contacted by your doctor through its toll-free number, 1-800-567-2028. Your urologist will be provided with information about the therapy as well as purchase instructions.
Web Reference: Bioniche, Inc.
Silver nitrate is an "antiseptic" bladder wash that is now rarely, if ever, used for IC. Why? When silver nitrate first became popular, doctors believed that it would destroy any bacteria or infection that could be triggering IC. However, we now know that IC is not bacterial in nature. Rather, IC is much more like a wound struggling to heal. Our goal in therapy is to soothe the bladder, not irritate it further. If your physician is suggesting silver nitrate, we strongly encourage you discuss the use of a "rescue instillation" and/or various oral medications first.
One of the most caustic medications placed in the bladder, silver nitrate actually damages (and/or strips off) the bladder lining. One of the most painful bladder instillations available, it is usually administered in a manner similar to that of DMSO or heparin, but under general anesthesia.
Silver nitrate was thought to work by first attacking or stripping the bladder lining. It was believed to trigger the body's immune system to step in and start the healing process. These antiseptic chemicals are also antibacterial in that they kill organisms present in the bladder.
Some patients have been successfully treated with these drugs
but the frequent, painful treatments usually must be done under general
anesthesia-- which carries some risk. This cannot be used in people who
have urinary reflux, a condition in which urine flows backward up the
ureters and into the kidneys. With the recent increase in the number and
variety of other IC treatments available, this is now rarely used.
Clorpactin® (WCS-90) solutions are commonly used throughout the medical community as a lavage or wash that, at very low concentrations, can clean wounds, sinuses, and remove the necrotic debris from massive infections. During surgical procedures (i.e. appendix rupture), it is used as an irrigant because it kills bacteria, fungi, and some viruses. Recent research studies have shown that it also has effectiveness in the treatment of oral diseases, such as canker sores, gingivitis and periodontal disease.
Yet, for the past twenty years, incorrect information abut Clorpactin has circulated throughout the IC community that it is "bleachlike" probably from the similarity of its name to chlorine or Clorox. It has also been used by some physicians at a painful dosage that is not recommended by the company or early research.
Grannum Sant, MD and Dennis La Rock, in "Intravesical Therapies for Interstitial Cystitis" described the early use of Clorpactin® in the bladder. "The initial rationale for the use of Clorpactin in the 1950's was based on the similarity between the 'classic form' of interstitial cystitis with tuberculosis of the bladder. Clorpactin® was used to treat bladder tuberculosis and this led to its use in interstitial cystitis based on the unsubstantiated belief that IC is caused by unidentified bacteria." Yet, even in those earliest days, pain was a consideration that the manufacturer took very seriously. Alfred Globus, CEO of United- Guardian, Inc., offered "When Clorpactin® was first used in the bladder for tuberculosis cystitis, it was done with a 0 .33% solution. However, we found that this concentration was too high because it caused profound pain. However, most patients could tolerate a 0.2% solution much more comfortably and still receive the same results after a series of 4-6 weekly instillations. Therefore, we've only recommended the 0.2% concentration for use in the bladder."
Yet, during the 1970's, the treatment protocol for IC was dramatically changed when researchers in New Zealand began using a 0.4% solution as a single instillation in combination with a hydrodistention of the bladder, rather than doing weekly instillations at 0.2%. The New Zealand protocol was significantly more painful and also required general anesthesia. Not surprisingly, this new method & approach became popular in America where doctors at leading universities began using this "more efficient" method of delivery. Dr. Globus reiterated:
Why would it be done at the higher dose than at the lower dose? Some care providers would argue that it saved the cost of several office visits. Others would say that it was as equally effective as the lower dosage. We wonder, though, if the patient experience was disregarded. Would a patient agree to have a therapy that was very painful when a much less traumatic method of using the same medication was also available? Likely not. Dr. Globus continued "When I asked one doctor how his patients reacted to the 0.4%, he said that his patients had 'handled it.' I was surprised. Why do it at the high dose, when a lower dose can be just as effective and not as painful." Thus, the legitimate stories of excruciating procedures and pain became commonplace.
Read more about Clorpactin in the ICN Guest Lecture Series, which featured Alfred Globus
Bacillus Calmette Guerin
BCG is used in the treatment of bladder cancer and, for a brief time, was used to treat IC. In June of 1998, the first double blind placebo study research results were released by researchers at the Department of Urology, William Beaumont Hospital, Royal Oak, Michigan, USA. Peters, Diokno et al. (7) report a 60% BCG response rate. However, a much larger national study performed by the ICCTG found little effectiveness. It is now rarely used for IC.